In order to elucidate the origins of the catalytic power of transmethylation enzymes and to provide basic information for the design and synthesis of active effectors of these enzymes as drugs and pharmacological research tools, studies of the transition states for the action of various transmethylation enzymes and studies of some stable complexes of these enzymes, as well as studies of appropriate non-enzymic reactions will be conducted. The major experimental tools will be kinetic isotope effects of hydrogen, carbon, oxygen and sulfur. The techniques employed will be precision spectrophotometric kinetics, radiometric double-label competition methods and mass-spectrometric isotope-ratio competition methods. The results will be interpreted by the use of vibrational analysis of model transition states and reactants. Investigations will be conducted by quantum mechanical and empirical methods of transition-state force fields and other properties, of the energetics of distortion of reactants and transition states and of the interactions of ligands with the enzymes.